The development of strategies to prevent Alzheimer's disease (AD) and related dementing illnesses will depend on an understanding of the underlying pathologic processes. In recent years it has become apparent that in older persons, these illnesses are usually the result of two or more fundamental pathogenic processes, often interacting additively. This complexity has been recognized largely as a result of neuropathological research in the context of longitudinal epidemiologic projects such as the Nun Study and the Honolulu-Asia Aging Study (HAAS), both now completed. The proposed project will compile accrued data and images from 854 HAAS autopsies and approximately 500 Nun Study autopsies, develop a common dataset and archive of photographic images of brain sections, and will be employed in parallel assessments of newly revised neuropathologic criteria for the identification and measurement of the AD disease process, which will be compared to previous criteria. In addition, these same data will be utilized for in an in-depth analysis of the interdependent and independent roles of AD brain lesions and brain atrophy as proximate causal factors responsible for dementia. These efforts are expected to: (1) provide a foundation for future analytic use of the accrued resources of the two projects, (2) examine the likely impact and utility of the revised neuropathologic AD assessment criteria for future research addressing the dementing illnesses of late life, and (3) facilitate a conceptual convergence of our understanding of the causes and importance of brain atrophy from neuroimaging and neuropathological perspectives.